# Astrocytes, Glucose Detection, and Counter-Regulation

> **NIH NIH R01** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2020 · $416,704

## Abstract

Project summary
 Glucose is the primary energy source for cellular metabolism. Thus, the maintenance of serum glucose
levels is critical for survival. Glucoprivation triggers defensive physiological and behavioral mechanisms that
are aimed at mobilizing stored carbohydrate during periods of fasting and physiological emergency.
 A critical site for the defense against glucopenia is the caudal medulla. This region contains at least two
potential detection/ effector control sites; the nucleus of the solitary tract (NST) and the ventrolateral medulla
(VLM). Both regions are important to physiological and behavioral responses to hypoglycemia. These
defensive counter-regulatory responses (CRR) include increases in serum glucagon and corticosteroids,
increased food intake, an increase in adrenergic tone, and a dramatic acceleration in gastric motility.
 Recent controversial data suggest that detection of a low glucose state by brainstem astrocytes could be
critical to the initiation of CRR. For example, transgenic mice whose GLUT2 transporter (critical component of
most glucodetection mechanisms) is knocked out do not demonstrate CRR. However, CRR defects are
rescued by the selective re-expression of GLUT2 in astrocytes, but not neurons. Our recent calcium (Ca++)
imaging studies demonstrated that astrocytes in NST increase cytoplasmic Ca++ in response to cyto-
glucopenia. Our in vivo, neurophysiological studies showed that glucoprivic challenges alter the sensitivity of
medullary vago-vagal reflex neurons, resulting in an increase in gastric motility. This modulatory effect on NST
neurons appears to be dependent on normal, functioning astrocytes. Studies in intact animals verified that both
dorsal medullary and systemic glucoprivation significantly increases gastric motility. Significantly, astrocyte
inactivation blocked this gastric component of CRR. These results explain century-old observations connecting
hypoglycemia with increased gastric motility and accelerated digestion in CRR. We will now address questions
relevant to broader aspects of astrocyte involvement in glucopenia defense.
 We hypothesize that intact hindbrain astrocyte signaling is essential to counter-regulatory control over not
only gastric motility, but other aspects of CRR such as the initiation of glucoprivic feeding and the critical and
rapid hormonal changes that provide a physiological defense against hypoglycemia. The pathways and
mechanisms connecting glucodetection and triggering defensive counter-regulatory responses are not well
understood. The role of the astrocyte in the CRR trigger mechanism is not understood at all. However, a
discovery that astrocytes serve as the critical initiators of CRR will significantly advance understanding gluco-
regulatory mechanisms and provide the basis for work on astrocyte involvement in pathological dysfunction of
CRR, especially hypoglycemia-associated autonomic failure (HAAF). The mechanism and relevance of
astrocyte glucodetection and...

## Key facts

- **NIH application ID:** 9994762
- **Project number:** 5R01DK108765-05
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Richard C. Rogers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,704
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994762

## Citation

> US National Institutes of Health, RePORTER application 9994762, Astrocytes, Glucose Detection, and Counter-Regulation (5R01DK108765-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994762. Licensed CC0.

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